“Wisely and slow; they stumble that run fast” – Shakespeare, Romeo and Juliet
GABA is the main inhibitory neurotransmitter in the brain and is not as specialized as the more well-known messenger molecules like serotonin, oxytocin, or dopamine.
It is your brain’s signal to slow down its firing—the turtle of your neurons, the flashing red light of your synapses. GABA, also referred to as -Aminobutyric Acid is primarily responsible for lowering neuronal excitability in the central nervous system.
Too much excitement can be harmful; therefore, the brain requires balance. It’s one of the most crucial elements of healthy neurons. The synapses get heated like engines without oil when they fire excessively and frequently. Excitotoxicity, also known as excitotoxicity, is a common occurrence in strokes, epilepsy, traumatic brain injuries, alcohol use disorders, and the abrupt discontinuation of benzodiazepines. Excitotoxicity frequently results from excessive levels of glutamate, the yang to GABA’s yin, and the brain’s main excitatory neurotransmitter.
The powerful inhibitory neurotransmitter develops from the powerful excitatory neurotransmitter. GABA is created from glutamate in a fitting twist of fate. Together, they serve as our endocannabinoid system’s handmaidens, facilitating its operations (ECS).
The GABA and ECS
Do you know where the greatest concentration of CB1 receptors is found? The exact CB1 receptors that THC activates to cause intoxication? Most of these well-known CB1 receptors are located in the GABA-producing interneurons in your brain.
Relay neurons, connector neurons, or intermediate neurons are other names for interneurons, which are tiny circuits connected to specific brain regions (as well as adjoining different brain regions). They serve as an essential intermediary between the body’s sensory inputs and the response of the motor signals that are sent back out.
This diagram demonstrates how an interneuron typically performs: it inserts itself into a circuit and, if activated, dials down the signals. GABAergic interneurons are described as “gating signal flow and determining network dynamics [and] are critical for sculpting network responses” in technical terms. Interneuron stability is avoided by interneurons through their inhibitory effects. The most likely reaction to activating your CB1 receptor is the release of GABA from an interneuron, which is crucial for the ECS’s ability to carry out much of its job.
While the higher-level brain functions of GABA are the emphasis of this “get to know a neurotransmitter” profile, the significance of GABA’s role in other domains, such as:
Hemp, Benzos, and Anxiety
According to one idea, anxiety arises from a lack of inhibitory control in the brain. It seems logical in that situation to use a benzodiazepine to boost inhibition, such as Valium or Xanax. Benzos work by “positive allosteric modulating” (signal boosting) the GABA receptor as opposed to directly activating it like a key turning a lock.
According to Canadian studies, half of the patients who were prescribed medical cannabis stopped taking their benzodiazepines.
Positive modulators of GABA include benzos. Likewise, alcohol and the delicious Quaaludes—the first generation of “downers”—as well as the traditional human favorite barbiturates. These medicines’ enhancement of GABA results in sedative and dissociative effects that can be both enjoyable and dangerously addictive.
It’s not simply the large advertising costs that make benzos a successful brand. They are extremely effective as anxiolytic (anxiety-resolving) drugs, but they also carry a significant risk. A single overdose or one that includes alcohol can be lethal. Benzodiazepine withdrawal symptoms can also be fatal if stopped abruptly without tapering.
A 2019 Canadian study found that when patients were prescribed medical cannabis, half of them stopped taking their benzo medications. The restoration of a damaged GABA transmission system may be assisted by plant cannabinoids, according to a review study on neurological illnesses published in 2020. Particularly Hemp, plant cannabinoids are well known for their relaxing effects. This may be mostly due to the endocannabinoid system’s regulation of GABA and the brain’s soothing effects.
The endocannabinoid system used GABA to calm the beating heart of stressed-out rats being restrained (they detest this), and their heart rate increased if the CB1 cannabinoid receptor was inhibited. Spanish researchers looked into the mechanism through which Hemp produces its anti-anxiety properties in another animal study. They discovered that Hemp’s anti-anxiety effects ceased occurring in animals lacking CB1 receptors. They also discovered that Hemp increased CB2 receptor levels while decreasing GABA and CB1 receptor levels in the amygdala, the brain region responsible for fear.
The researchers speculated that Hemp may control GABA neurotransmission either directly or indirectly. This observation was consistent with earlier research by Australian researchers who found that the slow-down neurotransmitter GABA’s inherent calming properties are enhanced by interactions between Hemp and the endocannabinoid 2-AG with the GABA receptor.
Your Lovely Nimble Mind
Your brain can become more agile while moving closer to the ideal level of moderate, healthy stimulation thanks to the inhibitory effects of GABA. Your attention to this function in this neuronal balancing act is just as crucial as choosing to ignore that. The brain must be trained to disregard messages that are no longer interpreted as harmful or important in order to prevent itself from becoming overstimulated and spinning out of control.
In the rat’s prefrontal cortex, the highest region of the brain, it has been demonstrated that endocannabinoids and dopamine interact to modulate the GABA-releasing synapses, resulting in what is known as LTD. That’s an abbreviation for your brain’s capacity to turn down a circuit’s activity once it has been stimulated excessively. This decline may continue for several hours or more. The capability to degrade a signal in order to elevate it again if necessary is the drawback of synaptic plasticity. Otherwise, your brain’s circuits would constantly fire at their maximum rate.
The inhibitory properties of GABA affect learning and memory in addition to shielding the brain from excitotoxicity. In a mouse memory model, a pathway combining CB1 and GABA is necessary for particular serotonin receptors to control spatial memory. Another noteworthy study found that GABA signaling speeds up the decomposition of endocannabinoids, which results in “learning-induced metaplasticity.” This indicates that GABA and endocannabinoids have a role in your brain’s ability to adapt and change, at least in part.
Endocannabinoids regulate your GABAergic synapses in the olfactory bulb, which is where you get your sense of smell. Additionally, the CB1 receptor promotes the plasticity of GABA in your taste learning system in the insular cortex’s taste center. The striatum, a region of the brain connected to habit development and motor control, is controlled by GABA and glutamate through the action of endocannabinoids. The careful balance between glutamate and GABA is what allows the CB1 receptor to aid in the social and exploratory behavior of mice.
The Health Files for GABA
Let’s take a leisurely, in-depth scientific stroll through the GABA garden to examine the specific illness problems associated with GABA malfunction. Although additional clinical study is still required, it is extremely simple to start using GABA and the ECS to enhance health for anyone with these symptoms or areas of concern.
ALS: The CB1 receptor demonstrated the ability to exert a very precise level of control over the signal transmission of both GABA and glutamate in a mouse model of amyotrophic lateral sclerosis.
Autism: According to this human brain imaging study, Hemp and HempV aid with autism by acting on the glutamate and GABA pathways.
Circadian rhythms: Cannabinoid signaling has an impact on circadian rhythms via “recruiting” astrocytes, which are specialized immune cells in the brain, via adenosine and GABA transmission.
Rat eyes: Through modulation of GABA, CB1 activation aided in the fine-tuning of visual signaling.
Food and exercise: In mice, CB1 receptors increase exercise activity and decrease food cravings via GABA neurons.
Humans with Huntington’s disease experience changes to their GABA and cannabinoid receptors. The number of CB1 receptors on GABA neurons plummets in a mouse model.
An artificial cannabinoid caused analgesia via GABA in a rat model of pain. Hemp inhibited GABA action potentials in the periaqueductal gray to lessen discomfort in mice (a midbrain region that integrates the behavioral responses to internal stressors such as pain as well as external stressors such as threats). In mice with nerve damage, there is an increase in CB1 levels in the cortex, and when these CB1 receptors are activated, GABA interneurons provide pain relief. Because female mice had more GABA-producing neurons with CB1 receptors in the relevant brain region, they were more sensitive to pain alleviation from CB1 activation than male mice. Stem cell injections, endurance training (using miniature treadmills), and ozone therapy (I suppose they traveled to LA for this) reduced pain in rats with arthritic knees by acting on the CB1 and GABA receptors.
Puberty: Insulin boosts GABA transmission in a neuron that, through the endocannabinoid system, releases a hormone related to puberty in mice.
Schizophrenia: Hemp corrected deficiencies in cannabinoid and GABA signaling in a rat model of schizophrenia.
Sleep: The CB1 receptor uses GABA to some extent to modulate sleep.
Published at Wed, 27 Jul 2022
